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Determinants of Mortality of Patients with COVID-19 in Wuhan, China: a Case-Control Study

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Determinants of Mortality of Patients with COVID-19 in Wuhan, China: a Case-Control Study 3950 Original Article Determinants of mortality of patients with COVID-19 in Wuhan, China: a case-control study Jian Li1#^, Luyu Yang2#, Qian Zeng3,4#, Qingyun Li5, Zhitao Yang6, Lizhong Han3,4, Xiaodong Huang7, Erzhen Chen6 1Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Department of ICU/Emergency, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China; 3Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 4Department of Clinical Microbiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 5Department of Respiration and Critical Care Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 6Emergency Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 7Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China Contributions: (I) Conception and design: E Chen, L Han, J Li; (II) Administrative support: E Chen, X Huang; (III) Provision of study materials or patients: L Yang, Q Li, Z Yang; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: J Li, Q Zeng; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. #These authors contributed equally to this work. Correspondence to: Erzhen Chen. Emergency Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Email: [email protected]; Lizhong Han. Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Clinical Microbiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Email: [email protected]; Xiaodong Huang. Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China. Email: [email protected]. Background: Coronavirus disease 2019 (COVID-19) has resulted in an overwhelmed challenge to the healthcare system worldwide. Methods: A case-control study of COVID-19 patients in Wuhan Third Hospital was conducted. 96 deceased COVID-19 patients and 230 discharged patients were included as the case group and control group, respectively. Demographic, epidemiological, clinical and laboratory variables on admission were collected from electronic medical records. Univariate and multivariate logistic regression were adopted to investigate the independent predictors of mortality. A nomogram was formed for predicting the mortality risk. Results: The multivariate stepwise logistic model demonstrated that age of 60+ years (OR =4.426, 95% CI: 1.955–10.019), comorbidity of cerebrovascular disease (OR =7.084, 95% CI: 1.545–32.471), white blood cell (WBC) count >9.5×109/L (OR =7.308, 95% CI: 1.650–32.358), platelet count <125×109/L (OR =5.128, 95% CI: 2.157–12.191), aspartate aminotransferase (AST) >40 U/L (OR =2.554, 95% CI: 1.253–5.206), cystatin C >1.1 mg/L (OR =4.132, 95% CI: 2.118–8.059), C reactive protein (CRP) ≥100 mg/L (OR =2.830, 95% CI: 1.311–6.109), creatine kinase isoenzymes (CK-MB) >24 U/L (OR =6.015, 95% CI: 2.119–17.07) and D-dimer >5 μg/L (OR =4.917, 95% CI: 1.619–14.933) were independent predictors of mortality of COVID-19 patients. The nomogram demonstrated a well discriminatory accuracy for mortality prediction with a C-index of 0.903. Conclusions: The determinants identified may help to determine patients at high risk of death at an early stage and guide the optimal treatment. Keywords: Coronavirus disease 2019 (COVID-19); mortality; determinant; case control study Submitted Oct 25, 2020. Accepted for publication Jan 21, 2021. doi: 10.21037/apm-20-2107 View this article at: http://dx.doi.org/10.21037/apm-20-2107 ^ ORCID: 0000-0003-0901-6458. © Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3937-3950 | http://dx.doi.org/10.21037/apm-20-2107 3938 Li et al. Determinants of mortality of patients with COVID-19 Introduction Guideline for the Diagnosis and Treatment of COVID-19 issued by the National Health Commission of the People’s Since December 2019, the pandemic of coronavirus disease Republic of China (v.5) as reported previously (14), and were 2019 (COVID-19), which originated from infection of laboratory-confirmed COVID-19. All deceased patients were severe acute respiratory syndrome coronavirus 2 (SARS- recruited into this study as the case group. Two discharged CoV-2), has spread around the world rapidly and raised patients to each deceased individual were randomly sampled serious concerns (1,2). COVID-19 has given rise to to be used as controls. Seven deceased patients were excluded an overwhelming destructive impact worldwide. As of from the study owing to non-accessibility of important 30 August 2020, the World Health Organization (WHO) laboratory findings and data of comorbidities, and 230 has reported a cumulative total of nearly 25 million discharged individuals were included in the study eventually. COVID-19 cases and 800,000 deaths globally (3). Regardless The Ethics Committees of Wuhan Third Hospitals has of the fact that the majority of confirmed patients were approved this study (No.: KY2020-007) and waived the considered to be mild or moderate, 5% were critical and individual informed consent due to the retrospective analysis. 14% severe on the basis of the largest survey of 72,314 The study was carried out in conformity to the Declaration patients to date (4). As with SARS-CoV (5) and Middle of Helsinki (as revised in 2013). East Respiratory Syndrome coronavirus (MERS-CoV) (6), COVID-19 is more easily predisposed to acute respiratory distress syndrome, respiratory failure, heart failure, Date collection septic shock and even death among susceptible cases (7). Data were gathered from April 28 to May 7, 2020. The Accumulated evidence from the latest studies indicates research team reviewed the medical records of COVID-19 the risk factors concerning fatality of COVID-19 are cases. A standardized case report form was adopted to collect heterogeneous and may include male, older age, comorbidity, the data of demographics, epidemiology, symptoms and signs, smoking, elevated D-dimer level, coagulopathy, neutrophilia laboratory and complication from electronic medical records, and organ dysfunction (8-13). However, most of those early and two experienced doctors cross-checked all of data. In case studies came from cases series and were descriptive analysis of unavailable epidemiological data or medical history from without consideration of adequate adjustment for potential medical records, researchers interviewed the patients or their confounding factors. So the estimations of risk factors of close relatives to further ascertain. If there was a discrepancy mortality were not very robust. Studies that address these between the medical records and the subjective description, limitations are necessary in order to explore the determinants data from medical records were used. Chest CT scan were of death for COVID-19 individuals. Therefore, a case- excluded from the analysis due to massive missing of CT data control study based on COVID-19 patients from 2 campuses at an early stage of the epidemic. of a designated hospital in Wuhan, Hubei province was conducted to identify the determinants of mortality of patients with COVID-19. We present the following article in Laboratory procedures accordance with the STROBE reporting checklist (available Laboratory method for confirming SARS-CoV-2 was at http://dx.doi.org/10.21037/apm-20-2107). reported elsewhere (1). Specifically, the Chinese Center for Disease Control and Prevention (CDC) and local CDC Methods were responsible for pathogen detecting. The real-time reverse transcription polymerase chain reaction assay (RT- Study design and participants PCR) was adopted to detect SARS-CoV-2 in oropharyngeal This case-control study enrolled COVID-19 patients with swab samples. The discharge criteria involved remission definite outcomes from 2 campuses (Shouyi campus and of respiratory symptoms, absence of fever for 3 days and Guanggu campus) of Wuhan Third Hospital. A total of above, completely improvement in bilateral lungs by chest 1,574 COVID-19 patients (1,241 in Guanggu and 334 in computed tomography (CT), and negative for 2 times in Shouyi) were admitted to this designated hospital from oropharyngeal swab specimens for SARS-CoV-2 RNA at 8 January 2020 to 17 March 2020. One hundred and three of least 1 day apart. Initial clinical laboratory examinations them (6.54%) were deceased and the rest of 1471 individuals included serum biochemical tests (including liver and were discharged. All patients were diagnosed following the kidney functions), complete blood count, coagulation © Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3937-3950 | http://dx.doi.org/10.21037/apm-20-2107 Annals of Palliative Medicine, Vol 10, No 4 April 2021 3939 profile, myocardial enzymes and D-dimer. Frequency of 96 cases had died during hospitalization, and 230 cases had examinations was placed under the discretion of doctors. recovered and been discharged. The median age of the 326 cases was 62 years (IQR 50–71; range, 25 to 98 years), and male accounted for 52.5% (Table 1); 133 (40.8%) cases Statistical analysis presented at least one comorbidity, with hypertension Continuous variables were expressed as median with being the most common comorbidity
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